Heavy water (D2O) is known to be lethal to humans and other life in large quantities. All I've been able to find on the toxicity is that it's similar to chemotherapy chemistry. I'd like to know precisely how having a single neutron in two atoms of an otherwise non-toxic molecule can cause the body to degrade. What's the root cause here?
2 Answers
The question is already answered by Armand. I am just going to elaborate on that by referencing the paper.
Different isotopes of chemical elements have slightly different chemical behaviors, but for most elements the differences are far too small to have a biological effect. In the case of hydrogen, differences in chemical properties among protium (light hydrogen), deuterium, and tritium occur, in part because chemical bond energy (the strength of a bond) changes with changed mass of the nucleus–electron system. The isotope effects are especially relevant in biological systems because of the prevalence of hydrogen atoms in biological molecules (even deuterated water can have significant effects in the human body).
Note that enzymes have a finely-tuned network of hydrogen bonds, both in the active center with their substrates, and outside the active center, to stabilize their tertiary structures. In a deuterated environment, some hydrogen bonds will be replaced with deuterium bonds which have different strength (Ref. 3), so normal reactions in cells can be disrupted.
Studies and experiments* show that heavy water affects cell division(mitosis), cell membrane changes and cellular heat stability, possibly as a result of inhibition of chaperonin formation. Also noted among the presumably wide-ranging cellular effects was the display of an altered glucose metabolism under deuterated condition in cells. $D_2O$ is more toxic towards at least some malignant cells, but the difference in sensitivity vs. normal cells does not seem high enough for therapeutic use.
In ref. 2, you will find a paper which shows the biochemical and pharmacological effects of heavy water on humans. Basically, to study the effects of heavy water on the metabolism humans, $D_2O$ and deuterated drugs were used and various changes were noted. Have a look for more details.
References
- Effect on biological systems (Wikipedia)
- Kushner DJ, Baker A, Dunstall TG. Pharmacological uses and perspectives of heavy water and deuterated compounds. Can J Physiol Pharmacol. 1999 Feb;77(2):79-88. PMID: 10535697.
- Steve Scheiner and Martin Čuma. Relative Stability of Hydrogen and Deuterium Bonds. J. Am. Chem. Soc. 1996 118, 6, 1511–1521 DOI: 10.1021/ja9530376
*Experiments with mice, rats, and dogs have shown that a degree of 25% deuteration causes (sometimes irreversible) sterility, because neither gametes nor zygotes can develop. Mammals (e.g. rats) were given heavy water to drink die after a week, at a time when their body water approaches about 50% deuteration. The mode of death appears to be the same as that in cytotoxic poisoning or in acute radiation syndrome , and is due to deuterium's action in generally inhibiting cell division.
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1$\begingroup$ Since "normal" water has around 156ppm of deuterium, and "D2O is more toxic towards malignant cells" does this imply a slightly beneficial effect of the normal deuterium found in water? $\endgroup$– MichaelSep 10, 2021 at 16:11
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1$\begingroup$ Great answer. It might make sense to add that the physiological effects are similar to those of chemotherapy (anti-cancer) drugs because chemo agents also disrupt cell division. $\endgroup$– zwolSep 10, 2021 at 18:58
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1$\begingroup$ At 50% deuteration, half of the molecules would be $HOD$, a quarter $H_2O$, and only a quarter $D_2O$. At 25% deuteration, only $\frac1{16}$ of molecules would be $D_2O$. $\endgroup$ Sep 12, 2021 at 3:30
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1$\begingroup$ @Acccumulation In the body, hydrogen atoms are constantly exchanging with or being incorporated into other molecules as well as water, so the calculation is not so simple. I'm not sure if the rat water deuteration reported above is a measured value or (as I suspect) a predicted or modeled value. $\endgroup$– ArmandSep 12, 2021 at 3:45
Substitution of deuterium atoms for normal hydrogen atoms changes structure and function at the atomic scale, disrupting normal biological processes. It causes changes in protein conformation and changes chemical reactions, as more and more $D$ replaces $H$, in water, substrates, macromolecules etc. "Stuff" doesn't work quite right and works less well the more the $D$. Remember, $D$ is roughly twice the mass of $H$, so it moves/diffuses very differently.
This QA at physlink.com reports:
The reason for these adverse effects is that replacing hydrogen with its heavier isotope deuterium slows down the rate of any chemical reaction in which the chemical bond to the hydrogen atom is broken.
(additional explanation at the link)
An actual scientific review, "Pharmacological uses and perspectives of heavy water and deuterated compounds" Kushner et al 1999 PMID: 10535697 seems to be pay-only access.